Can You Take Zaleplon Long‑Term?
No, zaleplon is FDA‑approved and guideline‑recommended only for short‑term use (2–4 weeks), not for long‑term daily therapy. 1, 2, 3 The American Academy of Sleep Medicine explicitly states that zaleplon carries "no short‑term usage restriction" in its labeling table, meaning it is intended for brief courses rather than chronic maintenance. 1 The FDA label and clinical trial data support efficacy for up to 35 nights, but evidence beyond 4 weeks is sparse, and regulatory guidance limits hypnotic use to short durations. 1, 2
Why Zaleplon Is Not Appropriate for Long‑Term Use
Regulatory and Guideline Restrictions
The FDA explicitly states that zaleplon and all benzodiazepine‑receptor agonists are intended for short‑term use only, typically ≤4 weeks for acute insomnia, because long‑term safety and efficacy data are insufficient. 1, 4
The American College of Physicians concludes there is insufficient evidence to determine the balance of benefits and harms of long‑term pharmacologic treatments for chronic insomnia, noting that few studies evaluated medications beyond 4 weeks. 4
The American Academy of Sleep Medicine recommends zaleplon 10 mg for sleep‑onset insomnia but does not endorse chronic daily use; the guideline positions zaleplon as a first‑line agent for short‑term symptom relief, not maintenance therapy. 1, 4
Limited Long‑Term Efficacy Data
The longest controlled trial of zaleplon lasted 35 nights, and even in that study, zaleplon 10 mg was significantly superior to placebo only on nights 29–30 (the primary endpoint), with earlier time points showing no sustained difference beyond the first 2 nights. 2
In 5‑, 14‑, and 28‑night polysomnographic studies, zaleplon reduced latency to persistent sleep on the first 2 nights, but at later time points all treatment groups—including placebo—showed reductions from baseline, eliminating the drug‑placebo difference. 2
Zaleplon's ultrashort half‑life (~1 hour) means it is designed to address sleep initiation only; it does not maintain therapeutic levels throughout the night, so sleep maintenance (total sleep time, number of awakenings) was not consistently improved versus placebo in clinical trials. 1, 2, 3, 5
Safety Concerns with Chronic Use
Complex sleep behaviors (sleep‑driving, sleep‑walking, sleep‑eating) can occur with zaleplon at any time during treatment, including after the first dose or any subsequent dose, and may result in serious injury or death. 2
The FDA warns that CNS‑depressant effects and next‑day impairment increase if zaleplon is taken with <7–8 hours of sleep remaining, at higher‑than‑recommended doses, or with other CNS depressants or alcohol; chronic use raises cumulative exposure to these risks. 2
Observational data link hypnotic use to increased fractures, major injuries, and possibly dementia, though these associations come primarily from benzodiazepine studies and causality remains unproven. 4
Tolerance to hypnotic effects generally did not occur during 5 weeks of zaleplon treatment in controlled trials, but data beyond 5 weeks are limited to small studies presented as abstracts, and the FDA has not approved long‑term use. 3
What Should Be Done Instead
First‑Line: Cognitive Behavioral Therapy for Insomnia (CBT‑I)
The American Academy of Sleep Medicine and American College of Physicians issue a strong recommendation that all adults with chronic insomnia receive CBT‑I as the initial treatment before or alongside any pharmacotherapy, because CBT‑I provides superior long‑term outcomes with sustained benefits after medication discontinuation. 1, 4
CBT‑I includes stimulus control (use bed only for sleep, leave bed if unable to fall asleep within ~20 minutes), sleep restriction (limit time in bed to approximate actual sleep time + 30 minutes), relaxation techniques, and cognitive restructuring of negative beliefs about sleep. 4
CBT‑I can be delivered via individual therapy, group sessions, telephone, web‑based modules, or self‑help books, all of which demonstrate comparable effectiveness. 4
Short‑Term Zaleplon Use (When Pharmacotherapy Is Necessary)
If CBT‑I is insufficient or unavailable, zaleplon 10 mg (5 mg for adults ≥65 years or those with hepatic impairment) may be prescribed for ≤4 weeks to address sleep‑onset insomnia. 1, 2
Zaleplon should be taken immediately before bedtime or after the patient has gone to bed and experienced difficulty falling asleep, with at least 4 hours remaining before planned awakening to minimize next‑day impairment. 2, 5
Reassess efficacy and adverse effects after 1–2 weeks; if sleep‑onset latency has not improved or if complex sleep behaviors occur, discontinue zaleplon immediately. 1, 2
Alternative Pharmacologic Options for Chronic Insomnia
For patients requiring longer‑term pharmacotherapy (>4 weeks), the American Academy of Sleep Medicine recommends switching to agents with better long‑term safety profiles:
Low‑dose doxepin 3–6 mg for sleep‑maintenance insomnia—reduces wake after sleep onset by 22–23 minutes, has minimal anticholinergic effects at hypnotic doses, and carries no abuse potential. 1, 4
Suvorexant 10 mg (orexin‑receptor antagonist) for sleep‑maintenance insomnia—reduces wake after sleep onset by 16–28 minutes and has a lower risk of cognitive and psychomotor impairment than benzodiazepine‑type agents. 1, 4
Ramelteon 8 mg (melatonin‑receptor agonist) for sleep‑onset insomnia—has no abuse potential, no DEA scheduling, and no withdrawal symptoms, making it appropriate for patients with substance‑use history. 1, 4
Eszopiclone 2–3 mg (1 mg for adults ≥65 years) for combined sleep‑onset and maintenance insomnia—increases total sleep time by 28–57 minutes and improves subjective sleep quality, though evidence beyond 4 weeks is limited and FDA labeling recommends short‑term use. 1, 4
Common Pitfalls to Avoid
Continuing zaleplon beyond 4 weeks without reassessment—FDA labeling and guideline evidence do not support routine long‑term use; if insomnia persists beyond 7–10 days, evaluate for underlying sleep disorders (e.g., sleep apnea, restless‑legs syndrome, circadian‑rhythm disorders). 1, 2
Failing to initiate CBT‑I before or alongside zaleplon—behavioral therapy provides more durable benefits than medication alone and facilitates eventual tapering. 1, 4
Using zaleplon for sleep‑maintenance problems—zaleplon's ultrashort half‑life (~1 hour) makes it ineffective for maintaining sleep throughout the night; switch to low‑dose doxepin or suvorexant for wake‑after‑sleep‑onset complaints. 1, 2, 5
Combining zaleplon with alcohol or other CNS depressants—markedly increases the risk of complex sleep behaviors, respiratory depression, and next‑day impairment. 2
Ignoring complex sleep behaviors—if a patient reports sleep‑driving, sleep‑walking, or sleep‑eating, discontinue zaleplon immediately and do not rechallenge. 2